A Clinical Study to Investigate the Effect of a Partially Hydrolysed Infant Formula With Added Synbiotics on Gut Microbiota Composition and Clinical Effectiveness in Infants at High Risk of Developing Allergy

• Infant formula with added synbiotics (Other): Intervention group: Infant Formula / Follow-On formula with partially hydrolysed cow's milk protein supplemented with prebiotics and probiotics.
• Standard infant formula (Other): Control group: Standard Infant Formula / Follow-On formula with intact cow's milk protein (only standard ingredients, without addition of pre- and probiotics).

Primary outcomes

• Faecel levels of Bifidobacteria [17 weeks]: Levels of Bifidobacteria at 17 weeks of age - stool sample

Secondary outcomes

• Faecal levels of Bifidobacteria and adult-like bacterial cluster [52 weeks]: Levels of Bifidobacteria and adult-like bacterial cluster up to 52 weeks of age - stool sample
• IgE-mediated allergic manifestations [52 weeks]: IgE-mediated allergic manifestations up to 52 weeks of age - blood sample

Sex: All, ages: any to 16 Weeks, accepts healthy volunteers

Inclusion Criteria:

1. Healthy term infants (gestational age ≥ 37 and ≤ 42 weeks) at high risk of developing allergy based on family history of allergy (*1).
2. Infants aged ≤ 16 weeks (max. 16 weeks + 0 days), preferably as soon as possible after birth.
3. Infants who start formula feeding within 16 weeks of age (infants of mothers who have chosen not to breastfeed or mothers who completely/partially cease breastfeeding before the subject's age of 16 weeks) (*2) OR Infants who are exclusively breastfed and whose mothers have the intention to exclusively breastfeed at least until their infant is 16 weeks of age (*2,3).
4. Written informed consent from one or both parents (according to local laws) and/or legal guardian.

1* Family history of allergy is defined as at least one first-degree relative (parent or full sibling) with self-reported historically doctor confirmed allergic disease (allergic rhinitis, asthma, food allergy, allergic eczema). In case of a self-reported historically non-doctor confirmed allergic disease, doctor confirmation must be done as part of the screening procedure according to local practice (e.g. skin prick test, IgE measurement).

2* Subjects whose mother intents to switch to formula feeding before the subject's age of 16 weeks but in the end still exclusively breastfeed, will be included in the breastfed reference group. The other way around, subjects whose mother intents to exclusively breastfeed for at least 16 weeks, but in the end decides to switch to formula earlier, will be included in the randomised groups. All these subjects should meet all other in-/exclusion criteria.

3* Exclusive breast feeding. WHO definition: only breast milk and no other liquids or solids except for drops or syrups consisting of vitamins, mineral supplements or medicines \[2\]. In addition to the WHO definition, in this study water is allowed as well as formula feeding during the first 72 hours of life.

* Exclusion Criteria:

  1. Consumption of any amount of infant formula based on intact protein before randomisation, except from consumption during the first 72 hours of life.
  2. Consumption of any amount of infant formula with added probiotics and/or probiotic supplement before randomisation.
  3. Existing allergic manifestations (e.g. allergic skin disorders, food allergy) before randomisation according to investigator's clinical assessment.
  4. Established or suspected cows' milk allergy, lactose intolerance, galactosaemia, or in infants on a fibre-free diet.
  5. Severe congenital abnormalities which could influence the subjects' growth (e.g. cystic fibrosis, bronchopulmonary dysplasia, tracheomalacia, tracheoesophageal fistula, major congenital heart disease, or any other condition according to investigator's clinical judgement).
  6. Severe neonatal illnesses (e.g. respiratory distress syndrome, severe sepsis intraventricular hemorrhage, severe neonatal jaundice, necrotizing enterocolitis, persistent pulmonary hypertension of the newborn, or any other condition which required to be treated with intravenous and/or intramuscular antibiotics).
  7. Known underlying disease predisposing to infection (e.g. HIV, viral hepatitis B, and C, auto-immune diabetes, immune deficiency).
  8. Severe renal failure and hepatic failure according to investigator's clinical judgement.
  9. Incapability of the parents to comply with study protocol or investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
  10. Participation in other studies involving investigational or marketed products concomitantly or within two weeks prior to screening visit.

• Results publication: Savova MV, Zhu P, Kindt A; TEMPO study team; Wopereis H, Belzer C, Harms AC, Hankemeier T. Fecal metabolome alterations in infants at risk of developing allergies during the first year of life. Metabolomics. 2026 Jul 1;22(4):112. doi: 10.1007/s11306-026-02478-6. PMID 42384241